Pregnancy: Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour

The aim of this study was to determine if nitric oxide (NO)production and nitric oxide synthase (NOS) isoforms change withinthe uterus and cervix during pregnancy and labour either atterm or preterm. NO production was compared in the rat uterusand cervix of non-pregnant and pregnant rats on days 18–22prior to labour, day 22 during delivery, 1 day post-partum andafter treatment with either 10 mg onapristone or progesterone.Uterine NO synthesis, reflected in nitrite production, increasedduring gestation (194.2±22.6 nmol/g on day 19) comparedwith the non-pregnant state (76.2±18.4 nmollg, P <0.05)and decreased during term labour and post-partum. Furthermore,injection of lipopolysaccharide (LPS) (100 µg/rat i.p.)on day 20 of gestation resulted in a significant increase inNO synthesis after 6 h. Conversely, cervical NO synthesis andnitrite production was low in the non- pregnant (65.1±9.2nmol/g) and pregnant animals on days 18–22 of gestation(53.2±9.0 nmol/g on day 22, P >0.05), but markedlyincreased during term labour (139±28.6 nmollg, P <0.05).Treatment with the antiprogestin onapristone suppressed uterineNO production and increased cervical production while continuousadministration of progesterone from day 19 had the oppositeeffect. LPS produced a significant increase in cervical NO production in both the pregnant (8-fold) and non-pregnant (4-fold)states. All three known NOS isofonus (i.e. iNOS, nNOS and eNOS)were detected in the cervical samples but only two were presentin the uterus (iNOS and eNOS). An increase in the presence ofiNOS occurred during labour at term compared with cervices collectedfrom day 19. This was contrary to the measurements of the isoformin the uterus. Also, there was a similar increase of nNOS inthe cervix during labour. This isoform seemed absent in theuterus during gestation. No significant changes occurred inthe abundance of eNOS in the cervix during labour at term comparedwith day 19. During preterm labour after onapristone, 1NOS concentrationsincreased significantly in the cervix. In order to examine whetherthe NO pathway plays a role in cervical ripening, the effectsof the nitric oxide synthesis inhibitor L-nitro-arginine methylester(L-NAME) on the duration of delivery and on cervical extensibilitywere also investigated. The duration of delivery was significantlyprolonged in L-NAME.treated rats compared with the control group(2.4-fold). Moreover, cervical extens ibifity decreased significantly(1.7-fold) after in-vitro incubation with L-NAME (P <0.005).We conclude that the NO system may have an active role in thecascade of processes involved in preparing the uterus and cervixfor parturitlon.